1. Field of the Invention
The present invention relates to a selective process for the preparation of basic coumarin derivatives and salts thereof which are formed by the reaction with organic and inorganic salts. The basic coumarin derivatives are represented by the formula: ##STR1## wherein R.sub.1 is selected from alkyl groups having basic substituents thereon such as piperidino ethyl, morpholino ethyl, diethylamino ethyl or diethylamino propyl; R.sub.2 is selected from the group consisting of hydrogen, alkyl and aryl groups; R.sub.3 is selected from the group consisting of alkyl radicals substituted with a basic group, an alkenyl group, a carboxy alkyl group or an alkoxy carbonyl alkyl group; and wherein X represents a halogen atom in the 8 position.
The process according to the present invention makes it possible to obtain as final products monohalogenated derivatives of 7-hydroxycoumarin of the formula: ##STR2## wherein X is as defined above. By virtue of the selective process which forms the compounds of the present invention in accordance with the objects of the present invention, it is certain that the halogen atoms are in position 8 in the final products. As will be shown hereinafter, the final products obtained in accordance with the present invention have a grade and purity sufficient to exercise a vasodilatory action effectively, in particular with respect to coronary vessels in animals and humans.
2. Prior Art
A pharmaceutical product under the generic name of "carbochromene" is already known which is represented by the general formula: ##STR3##
U.S. Pat. No. 3,515,721 discloses some mono- and di-halogen derivatives and method for forming the same which have the general formula: ##STR4##
These compounds also possess specific coronary vasodilatory activity but to a lower degree (see compound Nos. 4 and 10 in the included table), according to data furnished in the patent, with respect to carbochromene (compound No. 2 of the table).
Furthermore, in the above-mentioned patent, it is stated that there is obtained, in the case of monohalogenated derivatives, a single final product and only in the corresponding British specification No. 1,146,792 is it specified that the halogen is in position 8.
However, such a product is in fact composed of a mixture of derivatives of 7-hydroxy-coumarin and there are also present therein compounds having a halogen atom in the position indicated by X, i.e., position 8 or position 6.
The uncertainty as where the halogen is located is a result of the procedure used to make the compounds. Since the halogen is introduced during an intermediate phase of the process, it is not possible to determine with certainty what position will the halogen occupy.